The Interferon System: (1) To explore further our discovery that defective-interfering particles of vesicular stomatitis virus (VSV) which contain covalently linked message and anti-message (plus or minus) RNA do not kill cells, but are exquisitely efficient inducers of interferon, (2) To determine the nature of the interferon inducer moiety produced by defective-interfering particles of Sindbis virus, (3) To define the nature of the interferon-inducing particle in rabies virus stocks, (4) To determine why primary cells aged in vitro hyperproduce inteferon and an enhanced antiviral state upon appropriate treatment, and (5) To define the significance of interferon action in the inhibition of primary transcription in cells infected with certain negative-strand viruses. Cell Killing by Viruses: (1) To use temperature-sensitive mutants of VSV, Sindbis and NDV, selective inhibitors of macromolecular synthesis, and viral interference per se as probes to determine the role of cellular and viral factors in cell-killing by viruses, subviral components, and dsRNA of viral and synthetic origin, (2) To determine the nature and mode of action of putative cell killing factgr induced by VSV, and (3) To define the viral genes required for cell-killing by Sindbis and Newcastle disease viruses. Cell-Sparing: (1) To define the role of the interferon system and CPE-suppressing particles in the prevention of cell-killing by viruses, and (2) To determine the mechanism of virion self-induced cell-sparing. Persistent Infection: To define the role of interferon-inducing DI particles and ts-mutants, and CPE-suppressing particles in persistent infection.